Revisiting the concept of hepatosplenic schistosomiasis and its challenges using traditional and new tools

Different aspects of hepatosplenic schistosomiasis are revisited here. Manson's schistosomiasis causes periportal fibrosis and portal hypertension in approximately 6% of infected subjects, usually with preservation of their hepatic function. The assessment of liver involvement is of major importance in determining the prognosis and risk of complications from schistosomiasis, such as upper digestive bleeding secondary to variceal rupture. For many years, the diagnosis of hepatosplenic schistosomiasis and liver fibrosis was made by abdominal palpation and the finding of liver and/or spleen enlargement. However, there is no consensus regarding the clinical parameters of the liver and spleen to be considered in this physical evaluation. For the last three decades, abdominal ultrasound (US) has become the best imaging technique to evaluate liver fibrosis caused by schistosomiasis mansoni. However, US is a subjective procedure and is therefore examiner-dependent. Magnetic resonance imaging (MRI) findings have provided valuable information in addition to ultrasound and clinical examination. The combination of a comprehensive history and physical examination, basic laboratory tests (a stool examination for Schistosoma mansoni eggs and a blood cell count), biomarkers for liver fibrosis/portal hypertension and imaging methods seem to offer the best approach for evaluating patients with this disease. In situations where research is involved or in patients with severe disease, MRI may be considered.

Thrombocytopenia as a surrogate marker of hepatosplenic schistosomiasis in endemic areas for Schistosomiasis mansoni

Introduction This study aimed to evaluate whether a low platelet count is a good surrogate marker of hepatosplenic schistosomiasis (HSS) in a rural area of Brazil. A small district in southeastern Brazil, with a population of 1,543 individuals and a 23% prevalence of schistosomiasis, was selected for this investigation. Methods In July 2012, 384 volunteers were subjected to clinical, ultrasonography (US), and laboratory examinations, including stool sample analysis. The HSS patients were classified into four groups: Group 1 consisted of patients with a spleen >13cm and liver fibrosis; Group 2 consisted of patients with a palpable spleen and spleen>13cm measured by US; Group 3 consisted of patients with a spleen >13cm measured by US; and Group 4 consisted of patients with a palpable spleen. Results Eight patients were in Group 1 (2.1%), twenty-one were in Group 2 (5.5%), eight were in Group 3 (2.1%), and eighteen were in Group 4 (4.7%). A significant difference in the mean platelet counts was observed between the patients with and without HSS (p<0.01). Based on the receiver operating characteristic (ROC) curve (platelet count <143,000/mm3), the sensitivity was greater than 92% in all groups, and the specificity varied from 44.4% to 75%. Conclusions We concluded that in endemic areas, thrombocytopenia demonstrates good sensitivity for detecting HSS and may be used as a screening tool to identify patients with HSS.

The value of ultrasonography in assessment of portal hypertension in hepatosplenic schistosomiasis

Ultrasonography can reveal most of the manifestations of portal hypertension complicating hepatosplenic, schistosomiasis. However, direct demonstration of gastroesophageal varices by ultrasonography is still very difficult. An attempt was done to correlate sonographic features of portal hypertension with the degree of fibrosis to screen patients having varices and predicting their chance of bleeding. The results obtained were found to be consistent with the esophagogastric endoscopy and with history of hematemesis. Four parameters were used, size of spleen, degree of periportal fibrosis, presence of collaterals and portal vein diameter. A pilot field survey was also done adopting the same principle.

The spleen is an important site of T cell activation during human hepatosplenic schistosomiasis

We have undertaken a comparative immunephenotypic study of spleen cells from hepatosplenic patients (HS) and uninfected individuals (NOR) using flow cytometry. Our data did not show any significant differences in the mean percentage of T-cells and B-cells between the two groups. Analysis of activated T-cells demonstrated that HS present an increased percentage of CD3+HLA-DR+ splenocytes in comparison to NOR. Analysis of T-cell subsets demonstrated a significant increase on the percentage of both activated CD4+ T-splenocytes and CD8+ cells in HS. We did not find any difference in the mean percentage of CD28+ T-cells. Analysis of the B-cell compartment did not show any difference on the percentage of B1-splenocytes. However, the spleen seems to be an important reservoir/source for B1 lymphocytes during hepatosplenic disease, since after splenectomy we found a decreased the percentage of circulating B1-lymphocytes. We observed an increase on the percentage of CD2+CD3- lymphocytes in the spleen of HS suggesting that the loss of CD3 by activated T-cells or the expansion of NK-cells might play a role in the development/maintenance of splenomegaly.

The situation of hepatosplenic schistosomiasis in Brazil today

Specific chemotherapy against schistosomiasis together with environmental changes occurring in endemic areas of Brazil are causing a revolution in the clinico-pathological presentation of the disease when comparing to date from 10 to 15 years ago. To update the subject, an inquire was made among the most experienced Brazilian investigators in this field. They agree that a decrease of about 50 to 70% in prevalence, and an even higher decrease in incidence are taking place in Brazil today. The prevalence of schistosome-infection has decreased in some areas and increased in other, with spreading sometimes occurring to peri-urban regions, indicating that schistosomiasis control depends on the application of multiple measures. General clinical and pathological manifestations related to hepatosplenic disease, such as ascites, gastric hemorrhages, big-spleen syndrome, cor pulmonale, glomerulopathy, etc. are also less severe nowadays than they used to be in the past

Pathology of the spleen in hepatosplenic schistosomiasis. Morphometric evaluation and extracellular matrix changes

Histological, ultrastructural, morphometric and immunohistochemical data obtained from the study of spleens removed by splenectomy from 34 patients with advanced hepatosplenic schistosomiasis revealed that the main alterations were congestive dilatation of the venous sinuses and diffuse thickening of the splenic cords. Splenic cord thickening was due to an increase of its matrix components, especially type IV collagen and laminin, with the conspicuous absence of interstitial collagens, either of type I or type III. Deposition of interstitial collagens (types I and III) occurred in scattered, small focal areas of the red pulp, but in the outside of the walls of the venous sinuses, in lymph follicles, marginal zone, in the vicinity of fibrous trabeculae and in sidero-sclerotic nodules. However, fibrosis was not a prominent change in schistosomal splenomegaly and thus the designation "fibro-congestive splenomegaly" seems inadequate. Lymph follicles exhibited variable degrees of atrophy, hyperplasia and fibrous replacement, sometimes all of them seen in different follicles of the same spleen and even in the same examined section. Changes in white pulp did not seem to greatly contribute to increasing spleen size and weight, when compared to the much more significant red pulp enlargement.

Hepatosplenic schistosomiasis in field-based studies: a combined clinical and sonographic definition

A combined clinical and sonographic classification of hepatosplenic schistosomiasis mansoni to be used in field-based studies is proposed herein. Seven hundred forty one individuals out of 892 (83%), living in an area endemic for schistosomiasis in Brazil, have been ubmitted to clinical and ultrasound examinations. Based on two stool examinations the overall prevalence for schistosomiasis in this area was 73%. Abdominal palpation was performed with patients in dorsal decubit, during deep breath, by two experienced physicians and a portable ultrasound was used for the evaluation of liver fibrosis, portal collaterals and spleen size. Four groups of individuals were identified using data obtained by abdominal palpation and ultrasound examination: (1) palpable spleen and intense periportal thickening in 9 individuals (1.2%); (2) spleen not palpable and intense periportal thickening in 15 (2%); (3) palpable spleen with light to moderate periportal thickening in 32 (4.3%), and (4) palpable spleen with a normal liver on ultrasound in 30 (4%). The definition of hepatosplenic schistosomiasis in field-based studies as the finding of Schistosoma mansoni eggs in the stools in an individual with splenomegaly is not acceptable anymore. Abdominal ultrasound should be combined with clinical examination to accurately identify hepatosplenics in endemic areas for schistosomiasis.

Clinical versus ultrasound examination in the evaluation of hepatosplenic schistosomiasis mansoni in endemic areas

The best way to appraise the size of abdominal organs remains undefined. Herein we compare the size of liver and spleen in hepatosplenic schistosomiasis using clinical and ultrasound (US) examination, and the size of the organs measured by US with their visualization below the costal margin ("palpable by US"). For this study, 411 individuals from an endemic area for schistosomiasis mansoni in Brazil have been selected. We found that palpable spleens and left liver lobes are larger than non palpable ones. Also, 23% of normal spleens measured by US were palpable on clinical examination, and 22% of spleens increased in size on US were non palpable. A total of 21% of normal spleens were "palpable by US". We also found 54% of normal sized right liver lobes palpable on clinical examination, whilst 54% of the increased livers, measured by US, were non palpable. About 76% of normal right liver lobes were "palpable by US". We conclude that the association of clinical, ultrasound and magnetic resonance imaging (MRI) examinations, in the near future, should give the investigators the necessary tools to perform a more accurate clinical diagnosis of hepatosplenic schistosomiasis mansoni.

Imaging techniques and histology in the evaluation of liver fibrosis in hepatosplenic schistosomiasis mansoni in Brazil: a comparative study

Few publications have compared ultrasound (US) to histology in diagnosing schistosomiasis-induced liver fibrosis (LF); none has used magnetic resonance (MR). The aim of this study was to evaluate schistosomal LF using these three methods. Fourteen patients with hepatosplenic schistosomiasis admitted to hospital for surgical treatment of variceal bleeding were investigated. They were submitted to upper digestive endoscopy, US, MR and wedge liver biopsy. The World Health Organization protocol for US in schistosomiasis was used. Hepatic fibrosis was classified as absent, slight, moderate or intense. Histology and MR confirmed Symmers' fibrosis in all cases. US failed to detect it in one patient. Moderate agreement was found comparing US to MR; poor agreement was found when US or MR were compared to histology. Re-classifying LF as only slight or intense created moderate agreement between imaging techniques and histology. Histomorphometry did not separate slight from intense LF. Two patients with advanced hepatosplenic schistosomiasis presented slight LF. Our data suggest that the presence of the characteristic periportal fibrosis, diagnosed by US, MR or histology, associated with a sign of portal hypertension, defines the severity of the disease. We conclude that imaging techniques are reliable to define the presence of LF but fail in grading its intensity.

Hepatitis B and C virus markers among patients with hepatosplenic mansonic schistosomiasis

PURPOSE: To evaluate the frequency and the consequences of the co-infection of hepatitis B and C viruses in patients with hepatosplenic schistosomiasis (HSS). METHODS: B and C serologic markers, exposure to risk factors, biochemical assays, upper gastrointestinal endoscopies, and abdominal ultrasonograms were evaluated in 101 patients with HSS from 1994 to 1997. Whenever possible, PCR was tested and histopathological studies were reviewed. RESULTS: At least one HBV virus marker was found in 15.8%, and anti-HCV was detected in 12.9% of the subjects. The seropositive subjects tended to be older than the seronegative ones. A history of blood transfusion was significantly related to the presence of anti-HCV. Three (18.75%) out of 16 subjects exposed to B virus were HBsAg positive. Eleven (84.6%) out of thirteen patients who were anti-HCV positive demonstrated viral activity. Patients with ongoing viral infection presented a higher average level of liver aminotransferases, a higher frequency of cell decompensation and a higher rate of chronic hepatitis. Portal hypertension parameters were not influenced by viral exposure. CONCLUSIONS: The rate of hepatitis B and C viruses serologic markers observed in the patients with HSS was higher than the control group. The co-infection was responsible for a higher frequency of cell decompensation.

Portal hyperflow in patients with hepatosplenic mansonic schistosomiasis

PURPOSE: The purpose of this study was to assess portal hemodynamics in patients with portal hypertension due to hepatosplenic schistosomiasis as well as to assess the contribution of splanchnic hyperflow to the pathophysiology of the portal hypertension. METHODS: Sixteen patients with schistosomal portal hypertension and previous history of upper digestive bleeding due to esophageal varices rupture underwent elective esophagogastric devascularization and splenectomy and were prospectively studied. All patients underwent intraoperative invasive hemodynamic portal monitoring with a 4F-thermodilution catheter. The intraoperative portal hemodynamic assessment was conducted after laparotomy (initial) and after esophagogastric devascularization (final). RESULTS: The initial portal pressure was elevated (mean 28.5 ± 4.5 mm Hg), and a significant drop of 25% was observed at the end of the surgery (21.9 ± 4.9 mm Hg). The initial portal flow was elevated (mean 1766.9 ± 686.6 mL/min). A significant fall (42%) occurred at the end of the surgical procedure (1025.62 ± 338.7 mL/min). Fourteen patients (87.5%) presented a portal flow of more than 1200 mL/min, and in 5 cases, values greater than 2000 mL/min were observed. CONCLUSIONS: Esophagogastric devascularization and splenectomy promote a significant reduction of the elevated portal pressure and flow in schistosomal portal hypertension. These data favor the hypothesis of portal hyperflow in the physiopathology of portal hypertension of schistosomiasis.

Influence of the host related factors in the development of the hepatosplenic form of schistosomiasis mansoni

The frequency of hepatosplenomegaly in endemic areas is not proportional to the fecal ova count. This may be explained by epidemiological genetic. The occurrence of two or more cases of schistosomal hepatosplenomegaly in nuclear family is much higher than expected. The concentration is higher among siblings than it is among mothers and children of further and children. It is not significant between father and mother. If the mother, instead of the father has hepatosplenic schistosomiasis the relative risk for the child to acquire hepatosplenomegaly is at least five times (the maternal affect). The inbreeding is highler in the hepatosplenic than in the hepatointestinal patients. In some areas in Brazil the hepatosplenic form of the schistosomiasis mansoni occurs with much higher frequency in whites than in blacks. After treatment, reversion of hepatosplenic schistosomiasis occurs more frequently in non-whithers. It seems that the resistance of blacks to the hepatosplenic form of schistosomiasis may be related to the glyoxalase system , perhaps associated to another genetic marker. The hepatosplenic schistosomiasis is less frequent in longilineal individuals. In some areas the hepatosplenic form of schistosomiasis is more frequent in A blood group of ABO sistem. The family heredograms do not suggest a single mendelian inheritance, but probably a multifactorial and possibility poligenic one.